Protein Kinase C-γ and Calcium/Calmodulin-Dependent Protein Kinase II-α Are Persistently Translocated to Cell Membranes of the Rat Brain during and after Middle Cerebral Artery Occlusion

The levels of protein kinase C-γ (PKC-γ) and the calcium/calmodulin-dependent kinase II-α (CaMKII-α) were measured in crude synaptosomal (P2), particulate (P3), and cytosolic (S3) fractions of the neocortex of rats exposed to 1-hour and 2-hour middle cerebral artery occlusion (MCAO) and 2-hour MCAO followed by 2-hour reperfusion. During MCAO, PKC levels increased in P2 and P3 in the most severe ischemic areas concomitantly with a decrease in S3. In the penumbra, PKCγ decreased in S3 without any significant increases in P2 and P3. Total PKC-γ also decreased in the penumbra but not in the ischemic core, suggesting that the protein is degraded by an energy-dependent mechanism, possibly by the 26S proteasome. The CaMKII-α levels increased... (More)

The levels of protein kinase C-γ (PKC-γ) and the calcium/calmodulin-dependent kinase II-α (CaMKII-α) were measured in crude synaptosomal (P2), particulate (P3), and cytosolic (S3) fractions of the neocortex of rats exposed to 1-hour and 2-hour middle cerebral artery occlusion (MCAO) and 2-hour MCAO followed by 2-hour reperfusion. During MCAO, PKC levels increased in P2 and P3 in the most severe ischemic areas concomitantly with a decrease in S3. In the penumbra, PKCγ decreased in S3 without any significant increases in P2 and P3. Total PKC-γ also decreased in the penumbra but not in the ischemic core, suggesting that the protein is degraded by an energy-dependent mechanism, possibly by the 26S proteasome. The CaMKII-α levels increased in P2 but not P3 during ischemia and reperfusion in all ischemic regions, particularly in the ischemic core. Concomitantly, the levels in S3 decreased by 20% to 40% in the penumbra and by approximately 80% in the ischemic core. There were no changes in the total levels of CaMKII-α during MCAO. The authors conclude that during and after ischemia, PKC and CaMKII-α are translocated to the cell membranes, particularly synaptic membranes, where they may modulate cellular function, such as neurotransmission, and also affect cell survival. Drugs preventing PKC and/or CaMKII-α translocation may prove beneficial against ischemic cell death.

@article{2d9703f6-a4f1-489a-8cd1-6dc3a7b9b3ac,
abstract = {<p>The levels of protein kinase C-γ (PKC-γ) and the calcium/calmodulin-dependent kinase II-α (CaMKII-α) were measured in crude synaptosomal (P2), particulate (P3), and cytosolic (S3) fractions of the neocortex of rats exposed to 1-hour and 2-hour middle cerebral artery occlusion (MCAO) and 2-hour MCAO followed by 2-hour reperfusion. During MCAO, PKC levels increased in P2 and P3 in the most severe ischemic areas concomitantly with a decrease in S3. In the penumbra, PKCγ decreased in S3 without any significant increases in P2 and P3. Total PKC-γ also decreased in the penumbra but not in the ischemic core, suggesting that the protein is degraded by an energy-dependent mechanism, possibly by the 26S proteasome. The CaMKII-α levels increased in P2 but not P3 during ischemia and reperfusion in all ischemic regions, particularly in the ischemic core. Concomitantly, the levels in S3 decreased by 20% to 40% in the penumbra and by approximately 80% in the ischemic core. There were no changes in the total levels of CaMKII-α during MCAO. The authors conclude that during and after ischemia, PKC and CaMKII-α are translocated to the cell membranes, particularly synaptic membranes, where they may modulate cellular function, such as neurotransmission, and also affect cell survival. Drugs preventing PKC and/or CaMKII-α translocation may prove beneficial against ischemic cell death.</p>},
author = {Matsumoto, Shohei and Shamloo, Mehrdad and Matsumoto, Eriko and Isshiki, Atsushi and Wieloch, Tadeusz},
issn = {0271-678X},
keyword = {CaMKII,Cell death,Protein kinase C,Signal transduction,Stroke},
language = {eng},
number = {1},
pages = {54--61},
publisher = {Nature Publishing Group},
series = {Journal of Cerebral Blood Flow and Metabolism},
title = {Protein Kinase C-γ and Calcium/Calmodulin-Dependent Protein Kinase II-α Are Persistently Translocated to Cell Membranes of the Rat Brain during and after Middle Cerebral Artery Occlusion},
volume = {24},
year = {2004},
}